title: Protein expression patterns of ezrin are predictors of progression in T1G3 bladder tumours treated with nonmaintenance bacillus Calmette-Guérin.
abstract: BACKGROUND
  Bacillus Calmette-Guérin (BCG) is a standard treatment for reducing tumour recurrence and delaying progression of high-risk, non-muscle-invasive bladder tumours. However, it is not clear yet which patients are more likely to be responders to BCG.
  
  
  OBJECTIVE
  To evaluate the role of ezrin expression in bladder cancer (BCa) progression in T1G3 bladder tumours treated with BCG.
  
  
  METHODS
  Ezrin protein expression patterns were analysed on tumour specimens belonging to 92 patients with T1G3 non-muscle-invasive BCa undergoing nonmaintenance BCG treatment. Re-resection was not performed. The median follow-up was 90.5 mo (range: 3.0-173.0). A specific tissue array was created containing three representative cores of each of the tumour specimens belonging to these patients.
  
  
  METHODS
  Ezrin protein expression patterns were assessed by immunohistochemistry on this tissue array. Proliferation rates were assessed by means of Ki67 staining. Recurrence, progression into muscle-invasive tumours, and disease-specific overall survival (OS) rates were analysed using univariate and multivariate tests.
  
  
  CONCLUSIONS
  Among the 92 patients analysed, 40 recurred (43.5%), 17 progressed (18.5%), and 14 died of the disease (15.2%). Log-rank survival analyses revealed that an ezrin membrane expression <20% was significantly associated with increased progression (p=0.009) and shorter disease-specific OS (p=0.006). Multivariate analyses showed that ezrin was an independent prognostic marker of progression (p=0.031) and disease-specific survival (p=0.035). Interestingly, the low ezrin membrane expression correlated with high proliferation rates (p=0.033).
  
  
  CONCLUSIONS
  Immunohistochemistry analyses revealed that the membrane expression of ezrin is associated with the clinical outcome of patients with T1G3 tumours undergoing BCG treatment. Protein expression patterns of ezrin were associated with tumour progression in T1G3 disease. The differential expression of ezrin distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach.
authors.affiliation: Fundació Puigvert, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Palou
authors.forename: Ferrán
authors.initials: F
authors.lastname: Algaba
authors.forename: Irene
authors.initials: I
authors.lastname: Vera
authors.forename: Oscar
authors.initials: O
authors.lastname: Rodriguez
authors.forename: Humberto
authors.initials: H
authors.lastname: Villavicencio
authors.forename: Marta
authors.initials: M
authors.lastname: Sanchez-Carbayo
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000032:analysis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019459:Urothelium / Q000737:chemistry / Q000473:pathology; D000099149:Ezrin
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D000099149:Ezrin; C495901:TP53 protein, human